Introduction: Diabetes is the fastest growing chronic diseases worldwide and in Bosnia and Herzegovina. International standards for diabetes care have recognized the crucial role of pharmacists in diabetes management. Community pharmacists can provide services beyond medication dispensing inducing patient identification, assessment, education, referral, monitoring and behavioral counseling. Pharmacists’ attitudes toward diabetes are generally positive but do not correlate with the degree of their involvement in diabetes management and frequency of providing diabetes-related services varied throughout countries. Aim: To measure pharmacists’ attitude toward diabetes management and to identify pharmacy services that are currently provided to patients with diabetes. Material and Methods: We have conducted a descriptive, cross-sectional survey-based study among pharmacists from Bosnia and Herzegovina attending on of the conferences in May 2018. Majority of pharmacist attending such conferences are from community pharmacies across the whole country considering surveyed sample was representative. The questionnaire contained 3 different sections: a) participants’ demographics, b) measured participants’ attitude toward diabetes using the DAS-3 to measure participants’ degree of agreement to 33 diabetes-related statements, on a 5-point Likert type scale and c) a list of possible diabetes patient support activities that could be delivered by pharmacists based on authors experience and available literature. Results: The majority of respondents (86,5%) were female and 53,8% work in private owned pharmacies. Interest in diabetes was indicated by 94,2% while 59,6% completed special diabetes continuing education in the past. All the respondents expressed positive attitudes in all DAS-3 with no significant difference between overall DAS-3 and subscale values. Provided services differ but mainly drug oriented and partially include comorbidity counseling. Conclusion: Pharmacists had positive attitudes toward diabetes but they provided limited diabetes-related services to patients. Additional special education is needed.

Abstract Background Neuroendocrine carcinoma of the uterine cervix (NEC) is a rare cervical malignancy, accounting for 0.9% of all cervical carcinomas. Cervical NEC is a high-grade cancer with an aggressive clinical course and poor outcome. Given that no target therapy has been approved yet for NEC, we explored novel targetable biomarkers in a large cohort of NEC of the cervix. Methods Sixty-two NEC of the cervix were profiled for biomarkers of targeted therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), tropomyosin receptor kinases (NTRK1/2/3 gene fusions), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays. Results The study included 36 primary and 26 metastatic cervical NEC. The mean patient’s age was 43.6 years (range, 24-82 years). DLL3 expression was observed in 81% of the cases with 49% of cases expressing diffusely (≥50% of positive cancer cells) DLL3 protein. DLL3 expression was inversely correlated with commonly observed mutations: PIK3CA (7/47) (p = 0.018) and PTEN mutations (5/40) (p = 0.006). Other frequently seen mutations (TP53 17%, KRAS 11% and CTTNB1 5%) were not associated with DLL3 expression. PD-L1 expression, high TMB and MSI-H were seen in single cases. Although NTRK protein expression was observed in 21% of the cases, none of these had confirmatory NTRK gene fusions. TROP-2 and FOLR1 were negative in all tested cases. Conclusions DLL3 protein and PIK3CA/PTEN pathway genes may be potential therapeutic targets for a substantial proportion of the patients NEC of the cervix. Based on I-O biomarkers status, the patients with cervical NEC are less likely to benefit from immune checkpoint inhibitors. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure D. Arguello: Full / Part-time employment: Caris Life Sciences. E. Contreras: Full / Part-time employment: Caris Life Sciences. Z. Gatalica: Full / Part-time employment: Caris Life Sciences. All other authors have declared no conflicts of interest.

The purpose of the credit scoring process is the classification of the loan as default or non-default trying to reduce the risk for financial institutions. Paper aims to illustrate the implementation of a credit scoring model using boosting techniques. Specifically, the proposed solution is implemented using XGBoost algorithm discussing the role of hyperparameter tuning and feature selection in result optimization. Data used for obtaining performance scores is real-world data provided by a microfinance institution based in Bosnia and Herzegovina. Results suggest that significant optimization of XGBoost may be performed, yet, the model fails to outperform typically recommended approaches for solving credit scoring problem. Given that, it is suggested that although boosting techniques are increasingly being relied upon, it is unaccountable to make a decision without understanding the specificity of data and questioning whether other techniques are more suitable.

This article presents an overview of integrability of procedural modeling techniques needed to create a complete virtual city with streets, roads, building lots, exteriors and interiors with arranged furniture. Techniques are distributed into four hierarchies: urban plan, buildings, interior and furniture. Each technique is analyzed from the aspect of control of space definition, style uniformity, automatic interaction with other hierarchies and ability to procedurally generate a result around existing content. Each paper presented in this survey contributes either as a new control feature that has a potential of integrating with other techniques of higher, lower or same level of hierarchy, or as a new important part for creating a complete procedural city from highest to lowest level of hierarchy. The paper is concluded with a discussion of strong links between each area in the chain and important challenges in procedural generation of a complete city.

Creating school timetables is a problem whose complexity varies depending on school size and the requirements that occur in a model. The topic of this paper is related to schools that lack resources because they work in shifts and they are rarely discussed in literature. The first problem is the way the requirements are written. The paper deals with the XHSTT format and REDOSPLAT, a domain-specific language designed to set up timetable requirements. Another problem is the way a model is solved. We investigated the VNS and SVNS algorithms because they showed good results for this type of school. Their application on the actual test cases also revealed some interesting phenomena in formulating the requirements that can significantly affect the quality of the solution.

The application of the concept of software-defined networks (SDN) has, on the one hand, led to the simplification and reduction of switches price, and on the other hand, has created a significant number of problems related to the security of the SDN network. In several studies was noted that these problems are related to the lack of flexibility and programmability of the data plane, which is likely first to suffer potential denial-of-service (DoS) attacks. One possible way to overcome this problem is to increase the flexibility of the data plane by increasing the depth of programmability of the packet-switching nodes below the level of flow table management. Therefore, this paper investigates the opportunity of using the architecture of deeply programmable packet-switching nodes (DPPSN) in the implementation of a firewall. Then, an architectural model of the firewall based on a hybrid FPGA/CPU data plane architecture has been proposed and implemented. Realized firewall supports three models of DoS attacks mitigation: DoS traffic filtering on the output interface, DoS traffic filtering on the input interface, and DoS attack redirection to the honeypot. Experimental evaluation of the implemented firewall has shown that DoS traffic filtering at the input interface is the best strategy for DoS attack mitigation, which justified the application of the concept of deep network programmability.

A DNA marker-based study in European plum was performed within the project “Identification of a representative set of Prunus domestica accessions of European origin, well documented and characterized, to be included into the AEGIS system (PRUNDOC)”. A total of 46 local plum accessions from 10 European countries (Belgium, France, Germany, Greece, Italy, Latvia, Norway, Serbia, Slovakia and Sweden) were analysed using SSR loci. In addition, seven reference cultivars (Bistrica, Hanita, Mirabelle de Nancy, Reine Claude Violette, Stanley, Valor and Victoria) were analysed for standardization of allele sizes. The following nine primers were used; PacA33 is an EST-SSR developed in apricot, BPPCT039, BPPCT007, BPPCT014, BPPCT034, BPPCT040, UDP96 and UDP98 were developed from genomic peach DNA while CPSCT026 was developed from genomic DNA of Japanese plum Prunus salicina. None of the 46 investigated local plum accessions were identical, nor were any of them identical to any of the 7 reference cultivars. Genetic similarity among accessions was examined using Jaccard's similarity coefficients. The obtained dendrogram showed that the plum accessions did not group in a pattern corresponding to their country of origin.

Abstract The nuclear receptor chicken ovalbumin upstream promoter–transcription factor type II (COUP-TFII)/NR2F2 is expressed in adult Leydig cells, and conditional deletion of the Coup-tfii/Nr2f2 gene impedes their differentiation. Steroid production is also reduced in COUP-TFII–depleted Leydig cells, supporting an additional role in steroidogenesis for this transcription factor. COUP-TFII action in Leydig cells remains to be fully characterized. In the present work, we report that COUP-TFII is an essential regulator of the gene encoding the anti-Müllerian hormone receptor type 2 (Amhr2), which participates in Leydig cell differentiation and steroidogenesis. We found that Amhr2 mRNA levels are reduced in COUP-TFII–depleted MA-10 Leydig cells. Consistent with this, COUP-TFII directly activates a −1486 bp fragment of the mouse Amhr2 promoter in transient transfection assays. The COUP-TFII responsive region was localized between −67 and −34 bp. Chromatin immunoprecipitation assay confirmed COUP-TFII recruitment to the proximal Amhr2 promoter whereas DNA precipitation assay revealed that COUP-TFII associates with the −67/−34 bp region in vitro. Even though the −67/−34 bp region contains an imperfect nuclear receptor element, COUP-TFII–mediated activation of the Amhr2 promoter requires a GC-rich sequence at −39 bp known to bind the specificity protein (SP)1 transcription factor. COUP-TFII transcriptionally cooperates with SP1 on the Amhr2 promoter. Mutations that altered the GCGGGGCGG sequence at −39 bp abolished COUP-TFII–mediated activation, COUP-TFII/SP1 cooperation, and reduced COUP-TFII binding to the proximal Amhr2 promoter. Our data provide a better understanding of the mechanism of COUP-TFII action in Leydig cells through the identification and regulation of the Amhr2 promoter as a novel target.

Pulmonary embolism (PE) can lead to multi-organ damage including an acute renal dysfunction which is associated with adverse events and high long-term mortality rate. The aim of our study was to investigate the predictive role of renal dysfunction on intrahospital mortality risk in patients hospitalized due to PE. The study was performed in intensive care units of six university hospitals. The prospective cohort study comprised 665 consecutive patients with acute PE which was confirmed using MDCT. All patients underwent echocardiography examination on admission and blood samples were collected for troponin I (TnI), B-type natriuretic peptide (BNP) and routine laboratory analyses. Based on estimated glomerular filtration rate (GFR), patients were divided into three groups: first with the GFR <30ml/min, second with GFR 30–60 ml/min, and third with GFR >60 ml/min. During hospitalization in the first group the overall incidence of death was recorded in 28 (45.9%), in the second in 42 (18.9%), and in the third in 30 (7.9%) patients (p<0.0001). Pulmonary embolism as a cause of death was recorded in the first group in 18 (29.5%) patients, in the second in 25 (11.3%) and in the third in 17 (4.5%) patients (p<0.0001). Fatal bleeding was recorded in the first group in 1 (1.6%), in the second in 1 (0.5%) and in the third group in 3 (0.8%) patients (p<0.05). There were no significant differences regarding major bleeding frequency among the groups. Multivariate analysis showed that age, comorbidities, hemodynamic status, TnI, and GFR were strongly associated with an overall mortality rate and with death due to PE, while the use of anticoagulation therapy influenced the fatal bleeding rate. After controlling for age, we found that GFR on admission had a significant effect on in-hospital survival. Compared with patients in the third group, those from the second group had more than 2 fold increased mortality risk [OR 2.17 (CI 1.301–3.625), p=0.001], and patients in the first group had 6 fold higher risk of mortality [OR 6.006 (CI 3.487–6.006)]. In the ROC analysis GFR showed significant predictive value for intra-hospital mortality risk in PE patients [AUC= 0.725, 95% CI (0.68–0.78), p<0.001]. The highest sensitivity (64%) and specificity (70%) had GFR “cutoff” value of 59.12/min. Renal dysfunction, on admission, in patients with acute PE is strongly associated with high intrahospital mortality risk and fatal bleeding. The estimation of GFR in these patients is important not only for prediction of the outcome but also for the prevention of bleeding complications, regarding the optimal dosage of anticoagulants. Even though it seems that GFR calculation is not still the clinical routine in PE.

Results of currently available randomized trials have shown divergent outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The 2018 ESC/EACTS guidelines on myocardial revascularization do not recommend PCI in patients with diabetes and SYNTAX score ≥23. We aimed to compare the all-cause 4-year mortality after revascularization for complex coronary artery disease (CAD) in diabetics. The study group comprised consecutive diabetics with angiographically proven three-vessel CAD (≥50% diameter stenosis) and/or unprotected left main CAD (≥50% diameter stenosis) without major hemodynamic instability, who were treated in two institutions with PCI or referred for CABG between 2008 and 2010. All-cause mortality was ascertained by telephone contacts and/or from Mortality Registries. Using the hospital data system, 5145 patients were screened and 4803 elected not to follow the inclusion criteria. Out of 342 included patients, 177 patients underwent PCI and 165 patients were referred for CABG. Patients with whom CABG was performed were significantly older (64.69±8.8 vs. 62.6±9.4, p=0.03), more often on insulin treatment (91/165=55.2% vs. 26/177=14.7%, p<0.01), had more complex anatomical characteristics i.e. higher SYNTAX scores (32.5 IQR (15) vs. 18.0 IQR (15), p<0.01) and with left main stenosis (70/165=42.4% vs. 7/177=4.0%, p<0.01), compared to patients treated with PCI. The cumulative incidence rates of all-cause death were significantly different between PCI and CABG at 4 years (16/177=9.0% vs. 26/165=15.7%, respectively, log-rank p=0.03). There was a higher incidence of all-cause mortality in PCI patients with intermediate (23–32) and high (≥33) SYNTAX scores compared with those with low (0–22) SYNTAX scores (6/32=18.8% vs. 6/124=4.8%, log-rank p=0.01; 4/21=19.1% vs. 6/124=4.8%, log-rank p=0.02, respectively). On the contrary, patients who underwent CABG displayed similar morality rates irrespective of the SYNTAX scores (SYNTAX 0–22: 5/34=14.7%; SYNTAX 23–32: 9/54=16.7%; SYNTAX ≥33: 12/77=15.6%; log-rank p=0.9). Finally, when compared with CABG, more deaths were observed following PCI with intermediate and high SYNTAX scores (intermediate SYNTAX (23–32) PCI: 6/32=18.8% vs. CABG: 26/165=15.8%, log-rank p=0.94; high SYNTAX (≥33) PCI: 4/21=19.1% vs. CABG 26/165=15.8%, log-rank p=0.87). During a 4-year follow-up, CABG in comparison with PCI was associated with a higher rate of all-cause death, which can be accounted for by older age and comorbidities. In diabetics, our analysis is suggestive that PCI probably should be avoided in patients with SYNTAX ≥23, which is in concordance with the most recent guidelines. Individualized risk assessment as well as quantification of CAD by SYNTAX score remains essential in choosing appropriate revascularization method in patients with diabetes and complex CAD. None

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1Eurofarm Centar Medical Clinic, Sarajevo, Bosnia and Herzegovina 2Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina 3General Hospital Sarajevo, Sarajevo, Bosnia and Herzegovina KeYWORdS: heart failure, statin therapy, outcome. citAtiON: Cardiol Croat. 2019;14(9-10):222. | https://doi.org/10.15836/ccar2019.222 *AddReSS fOR cORReSpONdeNce: Amina Godinjak, Fra Anđela Zvizdovića 1, 71000 Sarajevo, Bosnia and Herzegovina. / Phone: +38761187010 / Email: aminagodinjak@gmail.com ORcid: Amina Godinjak, https://orcid.org/0000-0002-3697-8006 • Miralem Dešević, https://orcid.org/0000-0001-8760-6192 Amer Iglica, https://orcid.org/0000-0002-4677-8489 • Adis Kukuljac, https://orcid.org/0000-0002-4900-5094